tbuckley/cabot-search huggingface dataset:
PB2357: THE RELATIONSHIP BETWEEN SYMPTOM CLUSTERS AND QUALITY OF LIFE IN PATIENTS WITH HEMATOPOIETIC STEM CELL TRANSPLANTATION DURING EARLY TRANSPLANT: A LONGITUDINAL STUDY
Authors: F. Wu, A. Sun, X. Du, L. Gao
Journal: HemaSphere (2022)

Background: The conditioning regimen of haematopoietic stem cell trans-plantation (HSCT), a treatment common to haematological diseasesand malignancies, involves chemotherapy and/or total body irradiation. These treatments affect the patient profoundly due to theiradverse effects.monitor the dynamic changes of symptoms, analyze the cluster phenomenon, and explore the dynamic changes of symptom groups and their correlation with quality of life(QOL), in order to provide reference for medical staff to formulate efficient symptom management strategies. Aims: To investigate symptom clusters and in the HSCT patients at different time points in the early stage of transplant,and QOL. the correlation between was analyzed to provide the basis for clinical nurses to implement symptom manangement and improve the QOL. Methods: A total of 110 patients who received hematopoietic stem cell transplantation from August 2020 to February 2021 in a class Ⅲ hospital were selected as the study subjects.there were four times:on the day of admission,Pretreatment period(-4 to -3d),Myelosuppression(lowest count of WBC),Hematopoietic reconstitution period. The M.D.Anderson Symptom Inventory Blood and Marrow Transplantation (MDASI-BMT) module measured symptom severity. The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) measured QOL. Results: The main symptom clusters of hematopoietic stem cell transplantion patients in the early stage of transplantation mainly included somatic symptoms,gastrointestinal symptoms,psychological and emotional symptoms,and neurological symptoms.the composition of these symptoms was different at each time point.and the patients at different time points had different scores of QOL,the difference was statistically significant(P<0.05).the severity of the four symptom clusters were negatively correlated with the QOL scures at different times. Summary/Conclusion: In the early stage of transplantation,patients with multiple stable symptom cluster and sykptoms severity score were negatively correlated with QOL score.medical staff should manage the symptoms of patients in the early stage of transplantation,and carry out effective management to improve the QOL of patients.
PB2210: FAVORABLE OUTCOME AFTER SECOND CD19 CAR T INFUSION OF AN IDENTICAL PRODUCT: HOST ENVIRONMENT AND DISEASE CHARACTERISTICS DETERMINE THE OUTCOME OF TREATMENT
Authors: L. Frölich, V. Blumenberg, K. Rejeski, C. Schmidt, M. Winkelmann, F. Schöberl, L. von Baumgarten, W. Kunz, V. Bücklein, M. Subklewe
Journal: HemaSphere (2022)

Background: CD19-targeted CAR T cell therapy has revolutionized treatment options for patients with relapsed/refractory large B-cell lymphoma (r/r LBCL). However, a significant proportion of patients are refractory or relapse after treatment. So far, no consented treatment recommendations for patients failing CAR T cell therapy exist. Patients who relapse after initial response to therapy may be candidates for a second infusion, but data on the efficacy of this approach is still limited (Gauthier et al., Blood 2021). Aims: We sought to analyze differences in CAR T associated parameters that contribute to a favorable outcome after 2nd CAR T infusion of the identical CAR T product in a patient with r/r LBCL. Methods: Here, we present the clinical course of a 39-year-old patient with r/r LBCL, transformed from splenic marginal zone lymphoma (sMZL), who relapsed 11 months post their first CAR T cell infusion (CART1; October 2019) and received a second CAR T cell infusion afterwards (CART2; November 2020). Results: LBCL relapse was confirmed by histology, and IHC demonstrated positivity for CD19 and PD-L1. After lymphodepletion, the patient received a second dose (CART2; November 2020) of Tisagenlecleucel (Tisa-cel). Prior (day -27) and post (day 20) CART2 the patient received pembrolizumab (200 mg). Toxicity during CART1 was substantial, with ASTCT grade III CRS, grade I ICANS, and prolonged cytopenia (ANC <500/µl at day 90). After CART2 infusion, neither CRS nor ICANS were observed, and no longer-lasting cytopenias occurred. The patient achieved a CR following CART2, which has been ongoing for >15 months. Although CART1 and CART2 were identical products, derived from the same apheresis and production run, baseline proinflammatory markers (Ferritin) and tumor volume (LDH, MTV) differed between the two CART transfusions. The proinflammatory markers were significantly higher prior to CART1 vs CART2 (Ferritin 1582 vs 529 ng/ml) and the same trend was observed for tumor volume (LDH 262 vs 133 U/l; STLV 23,3 vs 2,6 cm3). Summary/Conclusion: Second CAR infusions represent a feasible salvage strategy in patients with late relapse after first CAR T infusion. The case illustrates that pretreatment factors, including patient inflammatory state and tumor volume may determine CAR T outcome in this setting. Peri-CAR-T checkpoint blockade may ameliorate tumor-intrinsic resistance mechanisms.
P1669: AUTOANTIBODY-MEDIATED PLATELET DESIALYLATION IN ADULTS WITH PRIMARY IMMUNE THROMBOCYTOPENIA
Authors: T. Schramm, C. Ungerböck, M. Fillitz, B. Dixer, D. Mehic, C. Ay, T. Backchoul, J. Zlamal, I. Pabinger, J. Gebhart
Journal: HemaSphere (2022)

Background: Primary immune thrombocytopenia (ITP) is an acquired thrombocytopenia. Its clinical symptoms are increased bleeding tendency and paradoxically also increased risk of thrombosis has been reported. Autoantibodies can bind and destruct platelet surface glycoproteins (GP), leading to Fc-independent platelet clearance. Refractory ITP patients show an increased tendency of platelet desialylation, whereas its impact on bleeding phenotype and thrombosis incidence is not completely elucidated yet. Aims: To link bleeding phenotype or thrombosis incidence to desialylated platelets in adults with primary ITP. Methods: Serum samples of 86 adult primary ITP patients and 20 healthy controls (HC) included in the Vienna ITP Biobank (EC 1843/2016) were analyzed. A lectin binding assay was performed to investigate the platelet desialylation status. Therefor healthy fresh washed platelets were incubated with patient or HC serum, stained with erythrina cristagalli lectin (ECL) and ricinus communis agglutinin (RCA) and analyzed via flow cytometry. Mean fluorescence intensity (MFI) cutoffs (ECL: MFI=1.43; RCA: MFI=1.10) were calculated based on HCs. Patients MFIs above the respective cutoffs were considered positive for lectin binding. Results: Table 1 depicts demographic and laboratory data of 86 primary ITP patients. Platelet desialylation with binding of ECL and/or RCA was detected in 9 (10.5%) out of 86 ITP patients (3 ECL only, 4 RCA only, 2 ECL and RCA). Of them, autoantibodies (AAbs) against GPIIb/IIIa were detected in 1 patient, whereas 5 patients did not express AAbs against GPIIb/IIIa or GPIb/IX and 3 patients had an unknown AAb status. The 2 ITP patients testing positive for binding both lectins were diagnosed with chronic ITP and did not express AAbs against GPIIb/IIIa or GPIb/IX. In comparison of patients with versus without platelet desialylation, no significant differences in relevant clinical characteristics, bleeding phenotype, or history of thrombosis were found (Table 1). Image:Summary/Conclusion: In 10.5% of the investigated patient cohort lectin binding was observed, representing mainly chronic ITP patients. No clear link of platelet desialylation with multi-refractory ITP, the bleeding phenotype or thrombosis history was found. The biobank from which this data derives is supported by Novartis, Swedish Orphan Biovitrum (SOBI), MedMedia Verlag und Mediaservice GmbH and AMGEN GmbH.
P936: TIME TO RESPONSE, DURATION OF RESPONSE, AND PATIENT-REPORTED OUTCOMES WITH DARATUMUMAB PLUS RD VS RD ALONE IN TRANSPLANT-INELIGIBLE PATIENTS WITH NDMM: SUBGROUP ANALYSIS OF THE PHASE 3 MAIA STUDY
Authors: T. Facon, S. K. Kumar, T. Plesner, P. Moreau, N. Bahlis, H. Goldschmidt, M. O’Dwyer, A. Perrot, C. P. Venner, K. Weisel, J. R. Mace, N. Raje, M. Tiab, M. Macro, L. Frenzel, X. Leleu, H. Pei, F. Borgsten, S. Z. Usmani
Journal: HemaSphere (2022)

Background: In the phase 3 MAIA study, adding daratumumab (DARA) to lenalidomide and dexamethasone (Rd) improved progression-free survival (primary endpoint), overall survival, duration of response, and patient-reported outcomes (PROs) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). Aims: Here we report a MAIA subgroup analysis of time to response, duration of response, and PROs. Methods: Transplant-ineligible patients with NDMM received 28-day cycles of Rd (R 25 mg PO on Days 1-21; d 40 mg PO QW) ± DARA (16 mg/kg IV QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W thereafter) until disease progression or unacceptable toxicity. Secondary endpoints included time to response and duration of response. PROs were measured using the EORTC QLQ-C30, with treatment effects assessed via mixed-effects model with repeated measures. Results: In total, 368 patients were assigned to the DARA plus lenalidomide and dexamethasone (D-Rd) group and 369 patients to the Rd group; 162 (44%) D-Rd patients and 142 (38%) Rd patients had renal impairment (defined as baseline CrCl ≤60 mL/min). At a 56.2-mo median follow-up, median times to very good partial response or better (≥VGPR) and complete response or better (≥CR) were shorter with D-Rd vs Rd in the overall study population and in the subgroups of patients with and without renal impairment (Table). Among patients who achieved ≥CR or partial response or better (≥PR), higher proportions of D-Rd vs Rd patients had not experienced disease progression at 48 mo (Table). Among patients with renal impairment, greater improvements from baseline in patient-reported pain, fatigue, and nausea and vomiting symptom scores were observed with D-Rd vs Rd across most timepoints; a notably greater meaningful reduction in pain symptom score was seen with D-Rd vs Rd as early as Cycle 6 Day 1 (least squares mean change from baseline, −14.9 vs −7.0; P=0.0241). Analyses for additional patient subgroups will be presented. Image:Summary/Conclusion: In transplant-ineligible patients with NDMM, D-Rd showed more rapid deep responses as well as more durable responses vs Rd, regardless of renal function. Improvements in patient-reported symptoms were generally greater with D-Rd vs Rd in patients with renal impairment. Our results support the use of D-Rd in transplant-ineligible patients with NDMM.
Abstract SY31-04: Uncovering targetable dependencies of latent brain metastatic cells
Authors: Srinivas Malladi
Journal: Cancer Research (2022)

Abstract Uncovering Targetable Dependencies of Latent Brain Metastatic Cells Srinivas Malladi, Department of Pathology, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, 75390, USA ABSTRACT HER2+ breast cancer patients presenting with brain metastases have poor survival outcomes. Metachronous brain metastases or relapse are observed in approximately fifty percent of HER2+ breast cancer patients considered disease free after a variable length of time post primary diagnosis and treatment. Disseminated latent residual cells that survive current therapies are responsible for these relapses or metachronous metastasis. How disseminated tumor cells survive as latent/dormant entities for extended period before initiating metachronous metastasis is poorly understood. Moreover, the basis for disparate metastatic fitness among disseminated tumor cells of similar oncotype within a distal organ is unknown and vital for better clinical management. Through a phenotypic screen in mice, we have isolated HER2+ latent (Lat) and brain metastatic (BM) cells.Transcriptomic and metabolic profiles of these brain-tropic breast cancer cells identified actionable dependencies and unique therapeutic opportunities. Brain-tropic Lat and metastatic cells have distinct metabolic profiles that determine their metastatic fitness. Both latent and metastatic cells survive in equilibrium with innate immune surveillance, oxidize glutamine and maintain cellular redox homeostasis through the anionic amino acid transporter xCT. Likewise, xCT expression was significantly higher in matched metachronous brain metastatic samples compared to primary tumors from HER2+ breast cancer patients. Genetic or pharmacological blockade of xCT eradicates residual disease and brain metastatic relapse in these preclinical models. Lactate secreted by aggressive metastatic cells limits innate immune surveillance and triggers overt metastasis. Furthermore, transcriptomic analysis identified augmented AXL expression. Depleting or inhibiting AXL in these HER2 targeted therapy resistant brain-tropic cells attenuates metastatic incidence. In sum, by investigating phenotypically distinct brain-tropic latent and metastatic cells, we uncovered the impact of metabolic diversity and adaptations on metastatic fitness and identified targetable vulnerabilities. Citation Format: Srinivas Malladi. Uncovering targetable dependencies of latent brain metastatic cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY31-04.
PB2344: RESILIENCE IN PATIENTS WITH LYMPHOID MALIGNANCIES: THE REPLY STUDY.
Authors: G. Dos Santos, V. Bogliacino, V. Irigoin, V. Toledo, P. Oldan, K. Blanco, P. Specht, A. Montaño, M. Posada, I. Alpire, D. Garrido, A. Alpuin, D. Villalvir, C. Guillermo
Journal: HemaSphere (2022)

Background: Resilience, the individual’s ability to maintain or restore psychological and physical functioning despite adversities and stressful life events, has became a matter of intense investigation in cancer research. In fact, resilience has emerged as a key element to understand differences in coping and adaptation during and/or after cancer treatment. Unfortunately, the evidence of its importance in hematologic and specifically in lymphoid malignancies is very scarce. Aims: The aims of this study were (a) to investigate the levels of resilience in patients with lymphoid malignancies, (b) to explore the relationship between resilience and quality of life and (c) between resilience and mental health outcomes, in a University Hospital in Montevideo, Uruguay. Methods: A cross-sectional, observational study was performed at the Hospital de Clinicas Dr. Manuel Quintela, assessing resilience in patients with lymphoid malignancies. The instruments Resilience Scale RS-14, Hospital Anxiety and Depression Scale (HADS) and EQ-5D-5L scale were used. Informed consent was obtained in all patients and the study was approved by the institutional ethics committee. Results: 105 patients were enrolled between July and December 2019: 76 NHL, 16 HL and 13 CLL. The median age was 53 and 53% of the patients were male. A remarkable high level of resilience was observed among the studied population, with a median resilience RS-14 score of 85,42 (IC 95%: 82,48 – 88,36). 95% of patients reported high or very high levels of resilience. No effects on resilience were found for gender, age, type of lymphoma or specific treatment. Resilience is positively correlated with quality of life (Spearman’s rho = 0.494, p< 0,001) and negatively with anxiety (-0,609, p<0,01) and depression (-0,537, p<0,001). To better study our lymphoma population, we considered our patients as high or low resilients if their RS-14 score was above or below the observed median, respectively. We found that our ‘high resilients’ showed a higher quality of life than our ‘low resilients’ (p<0,0001). Patients that did not report any issues in any of the dimensions of the EQ-5D-5L questionnaire (26,7%), showed a trend towards higher resilience scores (p=0.058). Summary/Conclusion: Resilience could be considered as a protective factor for patients with lymphoid malignancies. Stimulating resilience through specific interventions could positively impact their quality of life.
Association between the COVID-19 pandemic and pertussis derived from multiple nationwide data sources, France, 2013 to 2020
Authors: Soraya Matczak, Corinne Levy, Camille Fortas, Jérémie F Cohen, Stéphane Béchet, Fatima Aït El Belghiti, Sophie Guillot, Sabine Trombert-Paolantoni, Véronique Jacomo, Yann Savitch, Juliette Paireau, Sylvain Brisse, Nicole Guiso, Daniel Lévy-Bruhl, Robert Cohen, Julie Toubiana
Journal: Eurosurveillance (2022)

BackgroundInterventions to mitigate the COVID-19 pandemic may impact other respiratory diseases.AimsWe aimed to study the course of pertussis in France over an 8-year period including the beginning of the COVID-19 pandemic and its association with COVID-19 mitigation strategies, using multiple nationwide data sources and regression models.MethodsWe analysed the number of French pertussis cases between 2013 and 2020, using PCR test results from nationwide outpatient laboratories (Source 1) and a network of the paediatric wards from 41 hospitals (Source 2). We also used reports of a national primary care paediatric network (Source 3). We conducted a quasi-experimental interrupted time series analysis, relying on negative binomial regression models. The models accounted for seasonality, long-term cycles and secular trend, and included a binary variable for the first national lockdown (start 16 March 2020).ResultsWe identified 19,039 pertussis cases from these data sources. Pertussis cases decreased significantly following the implementation of mitigation measures, with adjusted incidence rate ratios of 0.10 (95% CI: 0.04-0.26) and 0.22 (95% CI: 0.07-0.66) for Source 1 and Source 2, respectively. The association was confirmed in Source 3 with a median of, respectively, one (IQR: 0-2) and 0 cases (IQR: 0-0) per month before and after lockdown (p = 0.0048).ConclusionsThe strong reduction in outpatient and hospitalised pertussis cases suggests an impact of COVID-19 mitigation measures on pertussis epidemiology. Pertussis vaccination recommendations should be followed carefully, and disease monitoring should be continued to detect any resurgence after relaxation of mitigation measures.
Apolipoprotein F is reduced in humans with steatosis and controls plasma triglyceride‐rich lipoprotein metabolism
Authors: Audrey Deprince, Nathalie Hennuyer, Sander Kooijman, Amanda C. M. Pronk, Eric Baugé, Viktor Lienard, An Verrijken, Eveline Dirinck, Luisa Vonghia, Eloïse Woitrain, Niels J. Kloosterhuis, Eléonore Marez, Pauline Jacquemain, Justina C. Wolters, Fanny Lalloyer, Delphine Eberlé, Sandrine Quemener, Emmanuelle Vallez, Anne Tailleux, Mostafa Kouach, Jean‐Francois Goossens, Violeta Raverdy, Bruno Derudas, Jan Albert Kuivenhoven, Mikaël Croyal, Bart van de Sluis, Sven Francque, François Pattou, Patrick C. N. Rensen, Bart Staels, Joel T. Haas
Journal: Hepatology (2022)

Background: NAFLD affects nearly 25% of the global population. Cardiovascular disease (CVD) is the most common cause of death among patients with NAFLD, in line with highly prevalent dyslipidemia in this population. Increased plasma triglyceride (TG)‐rich lipoprotein (TRL) concentrations, an important risk factor for CVD, are closely linked with hepatic TG content. Therefore, it is of great interest to identify regulatory mechanisms of hepatic TRL production and remnant uptake in the setting of hepatic steatosis. Approach and Results: To identify liver‐regulated pathways linking intrahepatic and plasma TG metabolism, we performed transcriptomic analysis of liver biopsies from two independent cohorts of obese patients. Hepatic encoding apolipoprotein F ( APOF ) expression showed the fourth‐strongest negatively correlation with hepatic steatosis and the strongest negative correlation with plasma TG levels. The effects of adenoviral‐mediated human ApoF (hApoF) overexpression on plasma and hepatic TG were assessed in C57BL6/J mice. Surprisingly, hApoF overexpression increased both hepatic very low density lipoprotein (VLDL)‐TG secretion and hepatic lipoprotein remnant clearance, associated a ~25% reduction in plasma TG levels. Conversely, reducing endogenous ApoF expression reduced VLDL secretion in vivo , and reduced hepatocyte VLDL uptake by ~15% in vitro . Transcriptomic analysis of APOF ‐overexpressing mouse livers revealed a gene signature related to enhanced ApoB‐lipoprotein clearance, including increased expression of Ldlr and Lrp1 , among others. Conclusion: These data reveal a previously undescribed role for ApoF in the control of plasma and hepatic lipoprotein metabolism by favoring VLDL‐TG secretion and hepatic lipoprotein remnant particle clearance.
PB2271: GERMLINE LOSS OF RHOG IDENTIFIES ITS ROLE AS AN ESSENTIAL REGULATOR OF HUMAN LYMPHOCYTE CYTOTOXICITY
Authors: A. Kalinichenko, G. P. Casoni, L. Dupré, L. Trotta, J. Huemer, D. Galgano, Y. German, B. Haladik, J. Pazmandi, M. Thian, Ö. Yüce Petronczki, S. C. Chiang, M. Taskinen, A. Hekkala, S. Kauppila, O. Lindgren, T. Tapiainen, M. J. Kraakman, K. Vettenranta, A. J. Lomakin, J. Saarela, M. R. Seppänen, Y. T. Bryceson, K. Boztug
Journal: HemaSphere (2022)

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of severe hyper-inflammation characterized by immune dysregulation and massive, aberrant activation of cytotoxic T cells and macrophages. While the molecular pathologies underlying secondary HLH are diverse, the primary or monogenic form of HLH is caused by the defects selectively disrupting perforin-mediated cytotoxicity in human lymphocytes. Aims: In our study we investigated the genetic etiology of and molecular pathomechanisms of the disease in a patient with for early-onset HLH. Methods: We applied a combination of state-of-the-art genetic and -omics technologies, including whole-exome sequencing (WES) and pharmacological screening combined with a wide range of cellular and molecular techniques to elucidate pathways underlying HLH pathology. Results: We investigated a patient with early-onset HLH who fulfilled all diagnostic criteria who was wildtype for mutations in any of the known HLH genes. We identified biallelic germline mutations in RHOG. Using genetic ablation of the RHOG in a model cell line and primary cytotoxic T lymphocytes (CTLs) from healthy individuals, we confirmed its crucial role in lymphocyte cytotoxicity. To decipher the underlying molecular pathomechanism, we defined the molecular partners of RhoG in human lymphocytes and discovered that RhoG interacts with the regulator of cytotoxic granule (CG) release Munc13-4 inducing docking of Munc13-4-positive CGs to the plasma membrane. This step is required for subsequent fusion of the membranes to release cytolytic cargo toward target cells. Using a pharmacological screening approach, we defined the molecular pathways perturbed in RhoG deficient lymphocytes and assessed in detail their impact on the cytoskeleton. Employing high-resolution microscopy, we showed that RhoG is essential for the reorganization of the synaptic F-actin and control of immune synapse architecture. We also demonstrated that cytoskeletal defects in RhoG deficient lymphocytes could be pharmacologically reconstituted. Thus, our results suggest a dual role of RhoG for CG exocytosis through regulation exocytosis and cytoskeletal machinery. Summary/Conclusion: Collectively, our work discovers a novel Mendelian disease affecting human immune function and homeostasis, potentially representing familial HLH type 6; defines molecular pathomechanisms of the discovered disorder; and identifies a novel layer of exocytosis and cytoskeleton regulation in human lymphocytes.